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Endothelial Cells Release a Chemoattractant for Retinal Pigment Epithelial Cells In Vitro

Endothelial Cells Release a Chemoattractant for Retinal Pigment Epithelial Cells In Vitro Abstract • Though the pathogenesis of choroidal neovascular membranes is uncertain, there is evidence to support a primary dysfunction in the retinal pigment epithelium (RPE). This suggests the possibility that a healthy RPE may provide a physical and/or chemical barrier to subretinal endothelial cell invasion. It has recently been shown that RPE cells in culture produce an inhibitor of neovascularization. Histopathologic evidence suggests that RPE cells tend to surround new blood vessels and contain them. We therefore investigated the possibility that RPE cells are guided toward endothelial cells by chemoattractants. Using a modified Boyden chamber technique, we showed that endothelial cells in culture produce a chemoattractant for RPE cells. The active component is trypsin sensitive, stable at extremes of pH (3 through 10), and nondialyzable (12,000- to 14,000-dalton cutoff). It is partially heat stable but becomes completely heat stable in the presence of 1% sodium dodecyl sulfate. These are all characteristics of the previously described endothelial cell-derived growth factor, suggesting that this mitogen might be the chemoattractant. The ability of RPE cells to be attracted to sites of new blood vessel formation may enhance their potential function as inhibitors of neovascularization. References 1. Estimated Statistics on Blindness and Related Problems . New York, National Society for the Prevention of Blindness, 1966, p 44. 2. Hyman L: Senile Macular Degeneration: An Epidemiologic Case Control Study, thesis, The Johns Hopkins University, Baltimore, 1981. 3. Gass JDM: Pathogenesis of disciform detachment of the neuroepithelium . Am J Ophthalmol 1967;63:573-711. 4. Sanders TE, Gay AJ, Newman M: Hemorrhagic complications of drusen of the optic disc . Am J Ophthalmol 1971;71:204-217. 5. Gass JDM, Wilkinson CP: Follow-up study of presumed ocular histoplasmosis . Ophthalmology 1972;76:672-694. 6. Gass JDM: Choroidal neovascular membranes: Their visualization and treatment . Ophthalmology 1973;77:310-320. 7. Gass JDM, Clarkson JG: Angioid streaks and disciform macular detachment in Paget's disease (osteitis deformans) . Am J Ophthalmol 1973;75:576-586. 8. Gerde LS: Angioid streaks in sickle cell trait hemoglobinopathy . Am J Ophthalmol 1974; 77:462-464. 9. Carlson MR, Kerman BM: Hemorrhagic macular detachment in the Vogt-KoyanagiHarada syndrome . Am J Ophthalmol 1977;84:632-635. 10. Deutman AF, Grizzard WS: Rubella retinopathy and subretinal neovascularization . Am J Ophthalmol 1978;85:82-87. 11. DeLacy JJ: Fluoroangiographic study of the choroid in man . Doc Ophthalmol 1978;45:168-209. 12. Lewis ML, Van Newkirk MR, Gass JDM: Follow-up study of presumed ocular histoplasmosis syndrome . Ophthalmology 1980;87:390-398.Crossref 13. Green WR, Key SN: Senile macular degeneration: A histopathologic study . Trans Am Ophthalmol Soc 1977;75:180-254. 14. Hogan MJ: Role of the retinal pigment epithelium in macular disease . Ophthalmology 1972;76:64-80. 15. Glaser BM, Campochiaro PA, Davis JL Jr, et al: Retinal pigment epithelial cells release an inhibitor of neovascularization . Arch Ophthalmol 1985;103:1870-1875.Crossref 16. Campochiaro PA, Jerdan JA, Glaser BM: Serum contains chemoattractants for human retinal pigment epithelial cells . Arch Ophthalmol 1984;102:1830-1833.Crossref 17. Fenselau A, Mello RJ: Growth stimulation of cultured endothelial cells by tumor cell homogenates . Cancer Res 1976;36:3269-3273. 18. Lowry DH, Rosebrough NJ, Farr AL, et al: Protein measurement with the folin phenol reagent . J Biol Chem 1951;193:265-275. 19. Gadjusek C, Dicorleto P, Ross R, et al: An endothelial cell-derived growth factor . J Cell Biol 1980;85:467-472.Crossref 20. DiCorleto PE, Gajdusek CM, Schwartz SM, et al: Biochemical properties of the endotheliumderived growth factor: Comparison to other growth factors . J Cell Physiol 1983;114;339-345.Crossref 21. Antoniades HN, Scher CD, Stiles CD: Purification of human platelet-derived growth factor . Proc Natl Acad Sci USA 1979;76:1809-1813.Crossref 22. Heldin CH, Westermack B, Wastesen A: Platelet-derived growth factor: Purification and partial characterization . Proc Natl Acad Sci USA 1979;76:3722-3726.Crossref 23. Raines E, Ross R: Platelet-derived growth factor: I. High-yield purification and evidence for multiple forms . J Biol Chem 1982;257:5154-5160. 24. Campochiaro PA, Glaser BM: Plateletderived growth factor is chemotactic for human retinal pigment epithelial cells . Arch Ophthalmol 1985;103:576-579.Crossref 25. Glaser BM, Kalebic T, Garbisa S, et al: Degradation of basement membrane components by vascular endothelial cells: Role in neovascularization , in Nugent J, O'Connor M (eds): Development of the Vascular System, Ciba Foundation Symposium 100 . Marshfield, Mass, Pitman Publishers Inc, 1983, pp 150-162. 26. Kalebic T, Garbisa S, Glaser BM, et al: Basement membrane collagen: Degradation of migrating endothelial cells . Science 1983;221:281-283.Crossref 27. Vidaurri-Leal J, Hohman R, Glaser BM: Effect of vitreous on morphologic characteristics of retinal pigment epithelial cells: A new approach to the study of proliferative vitreoretinopathy . Arch Ophthalmol 1984;102;1220-1223.Crossref 28. Gartner S, Henkind P: Pathology of retinitis pigmentosa . Ophthalmology 1982;89:1425-1432.Crossref 29. Del Monte MA, Maumenee IH, Green WR, et al: Histopathology of Sanfilippo's syndrome . Arch Ophthalmol 1983;101:1255-1262.Crossref 30. Lincoff H, O'Connor P, Bloch D: The cryosurgical adhesion: Part II . Ophthalmology 1970; 74:98-107. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Endothelial Cells Release a Chemoattractant for Retinal Pigment Epithelial Cells In Vitro

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Publisher
American Medical Association
Copyright
Copyright © 1985 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1985.01050120110030
Publisher site
See Article on Publisher Site

Abstract

Abstract • Though the pathogenesis of choroidal neovascular membranes is uncertain, there is evidence to support a primary dysfunction in the retinal pigment epithelium (RPE). This suggests the possibility that a healthy RPE may provide a physical and/or chemical barrier to subretinal endothelial cell invasion. It has recently been shown that RPE cells in culture produce an inhibitor of neovascularization. Histopathologic evidence suggests that RPE cells tend to surround new blood vessels and contain them. We therefore investigated the possibility that RPE cells are guided toward endothelial cells by chemoattractants. Using a modified Boyden chamber technique, we showed that endothelial cells in culture produce a chemoattractant for RPE cells. The active component is trypsin sensitive, stable at extremes of pH (3 through 10), and nondialyzable (12,000- to 14,000-dalton cutoff). It is partially heat stable but becomes completely heat stable in the presence of 1% sodium dodecyl sulfate. These are all characteristics of the previously described endothelial cell-derived growth factor, suggesting that this mitogen might be the chemoattractant. The ability of RPE cells to be attracted to sites of new blood vessel formation may enhance their potential function as inhibitors of neovascularization. References 1. Estimated Statistics on Blindness and Related Problems . New York, National Society for the Prevention of Blindness, 1966, p 44. 2. Hyman L: Senile Macular Degeneration: An Epidemiologic Case Control Study, thesis, The Johns Hopkins University, Baltimore, 1981. 3. Gass JDM: Pathogenesis of disciform detachment of the neuroepithelium . Am J Ophthalmol 1967;63:573-711. 4. Sanders TE, Gay AJ, Newman M: Hemorrhagic complications of drusen of the optic disc . Am J Ophthalmol 1971;71:204-217. 5. Gass JDM, Wilkinson CP: Follow-up study of presumed ocular histoplasmosis . Ophthalmology 1972;76:672-694. 6. Gass JDM: Choroidal neovascular membranes: Their visualization and treatment . Ophthalmology 1973;77:310-320. 7. Gass JDM, Clarkson JG: Angioid streaks and disciform macular detachment in Paget's disease (osteitis deformans) . Am J Ophthalmol 1973;75:576-586. 8. Gerde LS: Angioid streaks in sickle cell trait hemoglobinopathy . Am J Ophthalmol 1974; 77:462-464. 9. Carlson MR, Kerman BM: Hemorrhagic macular detachment in the Vogt-KoyanagiHarada syndrome . Am J Ophthalmol 1977;84:632-635. 10. Deutman AF, Grizzard WS: Rubella retinopathy and subretinal neovascularization . Am J Ophthalmol 1978;85:82-87. 11. DeLacy JJ: Fluoroangiographic study of the choroid in man . Doc Ophthalmol 1978;45:168-209. 12. Lewis ML, Van Newkirk MR, Gass JDM: Follow-up study of presumed ocular histoplasmosis syndrome . Ophthalmology 1980;87:390-398.Crossref 13. Green WR, Key SN: Senile macular degeneration: A histopathologic study . Trans Am Ophthalmol Soc 1977;75:180-254. 14. Hogan MJ: Role of the retinal pigment epithelium in macular disease . Ophthalmology 1972;76:64-80. 15. Glaser BM, Campochiaro PA, Davis JL Jr, et al: Retinal pigment epithelial cells release an inhibitor of neovascularization . Arch Ophthalmol 1985;103:1870-1875.Crossref 16. Campochiaro PA, Jerdan JA, Glaser BM: Serum contains chemoattractants for human retinal pigment epithelial cells . Arch Ophthalmol 1984;102:1830-1833.Crossref 17. Fenselau A, Mello RJ: Growth stimulation of cultured endothelial cells by tumor cell homogenates . Cancer Res 1976;36:3269-3273. 18. Lowry DH, Rosebrough NJ, Farr AL, et al: Protein measurement with the folin phenol reagent . J Biol Chem 1951;193:265-275. 19. Gadjusek C, Dicorleto P, Ross R, et al: An endothelial cell-derived growth factor . J Cell Biol 1980;85:467-472.Crossref 20. DiCorleto PE, Gajdusek CM, Schwartz SM, et al: Biochemical properties of the endotheliumderived growth factor: Comparison to other growth factors . J Cell Physiol 1983;114;339-345.Crossref 21. Antoniades HN, Scher CD, Stiles CD: Purification of human platelet-derived growth factor . Proc Natl Acad Sci USA 1979;76:1809-1813.Crossref 22. Heldin CH, Westermack B, Wastesen A: Platelet-derived growth factor: Purification and partial characterization . Proc Natl Acad Sci USA 1979;76:3722-3726.Crossref 23. Raines E, Ross R: Platelet-derived growth factor: I. High-yield purification and evidence for multiple forms . J Biol Chem 1982;257:5154-5160. 24. Campochiaro PA, Glaser BM: Plateletderived growth factor is chemotactic for human retinal pigment epithelial cells . Arch Ophthalmol 1985;103:576-579.Crossref 25. Glaser BM, Kalebic T, Garbisa S, et al: Degradation of basement membrane components by vascular endothelial cells: Role in neovascularization , in Nugent J, O'Connor M (eds): Development of the Vascular System, Ciba Foundation Symposium 100 . Marshfield, Mass, Pitman Publishers Inc, 1983, pp 150-162. 26. Kalebic T, Garbisa S, Glaser BM, et al: Basement membrane collagen: Degradation of migrating endothelial cells . Science 1983;221:281-283.Crossref 27. Vidaurri-Leal J, Hohman R, Glaser BM: Effect of vitreous on morphologic characteristics of retinal pigment epithelial cells: A new approach to the study of proliferative vitreoretinopathy . Arch Ophthalmol 1984;102;1220-1223.Crossref 28. Gartner S, Henkind P: Pathology of retinitis pigmentosa . Ophthalmology 1982;89:1425-1432.Crossref 29. Del Monte MA, Maumenee IH, Green WR, et al: Histopathology of Sanfilippo's syndrome . Arch Ophthalmol 1983;101:1255-1262.Crossref 30. Lincoff H, O'Connor P, Bloch D: The cryosurgical adhesion: Part II . Ophthalmology 1970; 74:98-107.

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Dec 1, 1985

References